Role of Two-Component System Response Regulator in the Antimicrobial Resistance, Virulence, Biofilm Formation, and Stress Response of Group B Streptococcus.

Authors:
Ying Yang
Ying Yang
National Research Institute for Family Planning
China
Mingjing Luo
Mingjing Luo
Key Laboratory of Zoonosis
Dr. Haokui Zhou, PhD
Dr. Haokui Zhou, PhD
CUHK
PostDoc
Bioinformatics
Hong Kong, Hong Kong | China
Carmen Li
Carmen Li
University of Alberta Edmonton
Canada
Alison Luk
Alison Luk
Ingham Institute for Applied Medical Research
Guoping Zhao
Guoping Zhao
Shanghai Institutes for Biological Sciences
China
Kitty Fung
Kitty Fung
Prince of Wales Hospital
Hong Kong
Margaret Ip
Margaret Ip
The Chinese University of Hong Kong
Hong Kong

Front Microbiol 2019 23;10:10. Epub 2019 Jan 23.

Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong.

Group B Streptococcus (GBS; ) is a leading cause of sepsis in neonates and pregnant mothers worldwide. Whereas the hyper-virulent serogroup III clonal cluster 17 has been associated with neonatal disease and meningitis, serogroup III ST283 was recently implicated in invasive disease among non-pregnant adults in Asia. Here, through comparative genome analyses of invasive and non-invasive ST283 strains, we identified a truncated DNA-binding regulator of a two-component system in a non-invasive strain that was homologous to , encoding the response regulator, which was conserved among GBS strains. Using isogenic knockout and complementation mutants of the ST283 strain, we demonstrated that resistance to bacitracin and the human antimicrobial peptide cathelicidin LL-37 was reduced in the Δ strain with MICs changing from 64 and 256 μg/ml to 0.25 and 64 μg/ml, respectively. Further, the ATP-binding cassette transporter was upregulated by sub-inhibitory concentrations of bacitracin in the wild-type strain. Upregulation of in the wild-type strain was also observed and thought to explain the increased resistance to antimicrobial peptides. DltA, an enzyme involved in D-alanylation during the synthesis of wall teichoic acids, which mediates reduced antimicrobial susceptibility, was previously shown to be regulated by the -type regulator in In a murine infection model, we found that the Δ mutation significantly reduced the mortality rate compared to that with the wild-type strain ( < 0.01). Moreover, this mutant was more susceptible to oxidative stress compared to the wild-type strain ( < 0.001) and was associated with reduced biofilm formation ( < 0.0001). Based on 2-DGE and mass spectrometry, we showed that downregulation of alkyl hydroperoxide reductase (AhpC), a Gls24 family stress protein, and alcohol dehydrogenase (Adh) in the Δ strain might explain the attenuated virulence and compromised stress response. Together, we showed for the first time that the regulator in GBS plays an important role in bacitracin and antimicrobial peptide resistance, virulence, survival under oxidative stress, and biofilm formation.

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https://www.frontiersin.org/article/10.3389/fmicb.2019.00010
Publisher Site
http://dx.doi.org/10.3389/fmicb.2019.00010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351488PMC
January 2019
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Sing. Med. J. 2002
Article in Performance Standards for Antimicrobial Susceptibility Testing. CLSI Document M100-S21 Twenty-First Informational Supplement.
Performance Standards for Antimicrobial Susceptibility Testing. CLSI Document M100-S21 Twenty-First Informational Supplement. 2011

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